The purpose of this project is to establish a breeding colony of Bassett Hound dogs with an immunodeficiency disease characterized by thymic, lymph node and splenic dysplasia; T lympohcyte dysfunction; low serum concentrations of IgG and IgA; and normal to elevated serum IgM. This represents a new animal model of variable, combined immunodeficiency disease. Initially, we will expand the breeding stock of these animals and undertake studies to establish the mode of inheritance, which is either X-linked or autosomal recessive. Structural and functional studies will be made to further delineate the pathogenesis of this condition. These will include fine structural investigations of the immune system; studies of in vivo responses to specific antigenic challenges and skin tests; determination of the ability of thymic and stem cell transplants to restore immunocompetency; and in vitro studies to enumerate circulating T and B lymphocyte populations and determine the ability of B lymphocytes to produce antigens, to examine T helper and suppressor-cell activities, and define the functional capabilities of the phagocytic system. The activity of enzymes involved in purine degradation in various cell populations will be determined using radiometric and spectrophotometric assays. Purine metabolites will be examined by high pressure liquid chromatography.